Separation of presynaptic Cav2 and Cav1 channel function in synaptic vesicle exo- and endocytosis by the membrane anchored Cak PMCA

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • Niklas Krick
  • Stefanie Ryglewski
  • Aylin Pichler
  • Arthur Bikbaev
  • Torsten Goetz
  • Oliver Kobler
  • Martin Heine
  • Ulrich Thomas
  • Carsten Duch
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000685035200012&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1073/pnas.2106621118
Externe Identifier
  • Clarivate Analytics Document Solution ID: UA3AR
  • PubMed Identifier: 34244444
ISSN
0027-8424
Ausgabe der Veröffentlichung
28
Zeitschrift
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Schlüsselwörter
  • synapse
  • Drosophila
  • Dmca1D
  • cacophony
  • PMCA
Artikelnummer
ARTN e2106621118
Datum der Veröffentlichung
2021
Status
Published
Titel
Separation of presynaptic Ca<sub>v</sub>2 and Ca<sub>v</sub>1 channel function in synaptic vesicle exo- and endocytosis by the membrane anchored Ca<SUP>k</SUP> PMCA
Sub types
  • Article
Ausgabe der Zeitschrift
118

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Abstract
<jats:title>Significance</jats:title> <jats:p> Synaptic vesicle (SV) release from presynaptic terminals requires nanometer precise control of action potential (AP)–triggered calcium influx through voltage-gated calcium channels (VGCCs). SV recycling also depends on calcium signals, though in different spatiotemporal domains. Mechanisms for separate control of SV release and recycling by AP-triggered calcium influx remain elusive. Here, we demonstrate largely independent regulation of release and recycling by two different populations of VGCCs (Ca <jats:sub>v</jats:sub> 2, Ca <jats:sub>v</jats:sub> 1), identify Ca <jats:sub>v</jats:sub> 1 as one of potentially multiple calcium entry routes for endocytosis regulation, and show functional separation of simultaneous calcium signals in the nanometer space of a presynaptic terminal by the plasma membrane calcium ATPase (PMCA). The Ca <jats:sub>v</jats:sub> 2/Ca <jats:sub>v</jats:sub> 1/PMCA functional triad may provide conserved means for independent control of different vital presynaptic functions. </jats:p>
Autoren
  • Niklas Krick
  • Stefanie Ryglewski
  • Aylin Pichler
  • Arthur Bikbaev
  • Torsten Götz
  • Oliver Kobler
  • Martin Heine
  • Ulrich Thomas
  • Carsten Duch
DOI
10.1073/pnas.2106621118
eISSN
1091-6490
ISSN
0027-8424
Ausgabe der Veröffentlichung
28
Zeitschrift
Proceedings of the National Academy of Sciences
Sprache
en
Online publication date
2021
Datum der Veröffentlichung
2021
Status
Published
Herausgeber
Proceedings of the National Academy of Sciences
Herausgeber URL
http://dx.doi.org/10.1073/pnas.2106621118
Datum der Datenerfassung
2022
Titel
Separation of presynaptic Ca <sub>v</sub> 2 and Ca <sub>v</sub> 1 channel function in synaptic vesicle exo- and endocytosis by the membrane anchored Ca <sup>2+</sup> pump PMCA
Ausgabe der Zeitschrift
118

Datenquelle: Crossref

Abstract
Synaptic vesicle (SV) release, recycling, and plastic changes of release probability co-occur side by side within nerve terminals and rely on local Ca<sup>2+</sup> signals with different temporal and spatial profiles. The mechanisms that guarantee separate regulation of these vital presynaptic functions during action potential (AP)-triggered presynaptic Ca<sup>2+</sup> entry remain unclear. Combining <i>Drosophila</i> genetics with electrophysiology and imaging reveals the localization of two different voltage-gated calcium channels at the presynaptic terminals of glutamatergic neuromuscular synapses (the <i>Drosophila</i> Ca<sub>v</sub>2 homolog, Dmca1A or cacophony, and the Ca<sub>v</sub>1 homolog, Dmca1D) but with spatial and functional separation. Ca<sub>v</sub>2 within active zones is required for AP-triggered neurotransmitter release. By contrast, Ca<sub>v</sub>1 localizes predominantly around active zones and contributes substantially to AP-evoked Ca<sup>2+</sup> influx but has a small impact on release. Instead, L-type calcium currents through Ca<sub>v</sub>1 fine-tune short-term plasticity and facilitate SV recycling. Separate control of SV exo- and endocytosis by AP-triggered presynaptic Ca<sup>2+</sup> influx through different channels demands efficient measures to protect the neurotransmitter release machinery against Ca<sub>v</sub>1-mediated Ca<sup>2+</sup> influx. We show that the plasma membrane Ca<sup>2+</sup> ATPase (PMCA) resides in between active zones and isolates Ca<sub>v</sub>2-triggered release from Ca<sub>v</sub>1-mediated dynamic regulation of recycling and short-term plasticity, two processes which Ca<sub>v</sub>2 may also contribute to. As L-type Ca<sub>v</sub>1 channels also localize next to PQ-type Ca<sub>v</sub>2 channels within axon terminals of some central mammalian synapses, we propose that Ca<sub>v</sub>2, Ca<sub>v</sub>1, and PMCA act as a conserved functional triad that enables separate control of SV release and recycling rates in presynaptic terminals.
Addresses
  • Institute of Developmental Biology and Neurobiology, Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
Autoren
  • Niklas Krick
  • Stefanie Ryglewski
  • Aylin Pichler
  • Arthur Bikbaev
  • Torsten Götz
  • Oliver Kobler
  • Martin Heine
  • Ulrich Thomas
  • Carsten Duch
DOI
10.1073/pnas.2106621118
eISSN
1091-6490
Externe Identifier
  • PubMed Identifier: 34244444
  • PubMed Central ID: PMC8285953
Funding acknowledgements
  • Deutsche Forschungsgemeinschaft: (Du 331-6/2
  • Deutsche Forschungsgemeinschaft: SFB1080/B12
  • Deutsche Forschungsgemeinschaft: SFB854/B08
Open access
true
ISSN
0027-8424
Ausgabe der Veröffentlichung
28
Zeitschrift
Proceedings of the National Academy of Sciences of the United States of America
Schlüsselwörter
  • Presynaptic Terminals
  • Motor Neurons
  • Synaptic Vesicles
  • Cell Membrane
  • Animals
  • Drosophila melanogaster
  • Calcium
  • Calcium Channels
  • Drosophila Proteins
  • Receptors, Glutamate
  • Probability
  • Endocytosis
  • Exocytosis
  • Action Potentials
  • Plasma Membrane Calcium-Transporting ATPases
Sprache
eng
Medium
Print
Open access status
Open Access
Paginierung
e2106621118
Datum der Veröffentlichung
2021
Status
Published
Publisher licence
CC BY-NC-ND
Datum der Datenerfassung
2021
Titel
Separation of presynaptic Ca<sub>v</sub>2 and Ca<sub>v</sub>1 channel function in synaptic vesicle exo- and endocytosis by the membrane anchored Ca<sup>2+</sup> pump PMCA.
Sub types
  • Research Support, Non-U.S. Gov't
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
118

Files

https://www.pnas.org/content/pnas/118/28/e2106621118.full.pdf https://europepmc.org/articles/PMC8285953?pdf=render

Datenquelle: Europe PubMed Central

Abstract
Synaptic vesicle (SV) release, recycling, and plastic changes of release probability co-occur side by side within nerve terminals and rely on local Ca2+ signals with different temporal and spatial profiles. The mechanisms that guarantee separate regulation of these vital presynaptic functions during action potential (AP)-triggered presynaptic Ca2+ entry remain unclear. Combining Drosophila genetics with electrophysiology and imaging reveals the localization of two different voltage-gated calcium channels at the presynaptic terminals of glutamatergic neuromuscular synapses (the Drosophila Cav2 homolog, Dmca1A or cacophony, and the Cav1 homolog, Dmca1D) but with spatial and functional separation. Cav2 within active zones is required for AP-triggered neurotransmitter release. By contrast, Cav1 localizes predominantly around active zones and contributes substantially to AP-evoked Ca2+ influx but has a small impact on release. Instead, L-type calcium currents through Cav1 fine-tune short-term plasticity and facilitate SV recycling. Separate control of SV exo- and endocytosis by AP-triggered presynaptic Ca2+ influx through different channels demands efficient measures to protect the neurotransmitter release machinery against Cav1-mediated Ca2+ influx. We show that the plasma membrane Ca2+ ATPase (PMCA) resides in between active zones and isolates Cav2-triggered release from Cav1-mediated dynamic regulation of recycling and short-term plasticity, two processes which Cav2 may also contribute to. As L-type Cav1 channels also localize next to PQ-type Cav2 channels within axon terminals of some central mammalian synapses, we propose that Cav2, Cav1, and PMCA act as a conserved functional triad that enables separate control of SV release and recycling rates in presynaptic terminals.
Autoren
  • Niklas Krick
  • Stefanie Ryglewski
  • Aylin Pichler
  • Arthur Bikbaev
  • Torsten Götz
  • Oliver Kobler
  • Martin Heine
  • Ulrich Thomas
  • Carsten Duch
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/34244444
DOI
10.1073/pnas.2106621118
eISSN
1091-6490
Externe Identifier
  • PubMed Central ID: PMC8285953
Ausgabe der Veröffentlichung
28
Zeitschrift
Proc Natl Acad Sci U S A
Schlüsselwörter
  • Dmca1D
  • Drosophila
  • PMCA
  • cacophony
  • synapse
  • Action Potentials
  • Animals
  • Calcium
  • Calcium Channels
  • Cell Membrane
  • Drosophila Proteins
  • Drosophila melanogaster
  • Endocytosis
  • Exocytosis
  • Motor Neurons
  • Plasma Membrane Calcium-Transporting ATPases
  • Presynaptic Terminals
  • Probability
  • Receptors, Glutamate
  • Synaptic Vesicles
Sprache
eng
Country
United States
PII
2106621118
Datum der Veröffentlichung
2021
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2021
Titel
Separation of presynaptic Cav2 and Cav1 channel function in synaptic vesicle exo- and endocytosis by the membrane anchored Ca2+ pump PMCA.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
118

Datenquelle: PubMed

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